BACAMPICILLIN
DESCRIPTION:
PENGLOBE (bacampicillin HCl) is a member of the ampicillin class of semi-
synthetic penicillins derived from the basic penicillin nucleus: 6-
aminopenicillanic acid. PENGLOBE, as well as ampicillin and other ampicillin
analogues, is acid resistant and suitable for oral administration.
PENGLOBE is the hydrochloride salt of 1-ethoxycarbonyloxyethyl ester of
ampicillin and is available as a tablet. During the process of absorption from
the gastrointestinal tract, PENGLOBE is hydrolyzed rapidly to ampicillin, a
well characterized and effective antibacterial agent. Each 400 mg tablet of
PENGLOBE is chemically equivalent to 280 mg of ampicillin.
Chemically, PENGLOBE is 1'-ethoxycarbonyloxyethyl - 6 - (D-alpha
aminophenylacetamide) - penicillinate hydrochloride. It has a molecular weight
of 501.96.
Inert ingredients for the tablets are: microcrystalline cellulose, lactose and
magnesium stearate. May also include the following: hydroxypropyl
methylcellulose; and opaspray white, opadry white and opadry clear (these
components may contain other inert ingredients).
ACTIONS/CLINICAL PHARMACOLOGY:
CLINICAL PHARMACOLOGY
PENGLOBE is characterized by its more complete and more rapid absorption from
the GI tract than ampicillin. PENGLOBE tablets of 400 mg, 800 mg, and 1600 mg
have provided ampicillin peak serum concentrations of 7.9, 12.9, and 20.1
mcg/mL. These peak levels are approximately three times the levels obtained with
administration of equivalent amounts of ampicillin. The areas- under-the-serum-
concentration curves obtained during the first 6 hours were 24.8 and 12.9
mcg/mL/hr., when bacampicillin HCl 800 mg and ampicillin 500 mg were
administered to adults. (See Graph.)
In fasting adult volunteers, a 400 mg dose of the tablet gave a peak serum
ampicillin concentration of 7.2 mcg/mL. In fasting pediatric patients a 12.5
mg/kg dose provided a peak of 8.4 mcg/mL.
After oral administration of PENGLOBE tablet, ampicillin activity in serum
peaks at 0.7-0.9 hours (compared to 1.5-2.0 hours after administration of
ampicillin). Serum ampicillin half-life is 1.1 hours after either PENGLOBE or
ampicillin administration.
Peak tissue and body fluid ampicillin concentrations also are higher after
administration of PENGLOBE. Utilizing a special skin window technique to
determine ampicillin levels, therapeutic levels in the interstitial fluid were
higher and more prolonged after PENGLOBE than after ampicillin administration.
PENGLOBE is stable in the presence of gastric acid. Food does not retard
absorption of PENGLOBE tablets which may be given without regard to meals.
PENGLOBE has been shown to be rapidly and well absorbed after oral
administration, with about 75% of a given dose being recoverable in the urine as
active ampicillin within 8 hours of administration. Urinary excretion can be
delayed by concurrent administration of probenecid. The active moiety of
PENGLOBE (i.e., ampicillin) diffuses readily into most body tissues and
fluids. In serum, ampicillin is only 20% protein-bound, compared to 60-90% for
other penicillins.
MICROBIOLOGY
PENGLOBE per se has no In Vitro antibacterial activity and owes its In Vivo
bactericidal activity to the parent compound, ampicillin. The ampicillin class
of penicillins (including PENGLOBE) has a broad spectrum of activity against
many gram-negative and gram-positive bacteria. Like other penicillins, the
ampicillin class of penicillins inhibits the synthesis of cell wall mucopeptide.
Ampicillin class antibiotics are inactivated by beta-lactamases produced by
certain strains of Enterobacter, Citrobacter, Haemophilus Influenzae, and
Escherichia Coli, and by most strains of staphylococci and indole-positive
Proteus spp. Ampicillin class antibiotics are not active against Pseudomonas,
Klebsiella, or Serratia spp.
SUSCEPTIBILITY TESTING
ELUTION TECHNIQUE: For the automated method of susceptibility testing (i.e.,
Autobac(TM)), gram- negative organisms should be tested with the 4.5 mcg
ampicillin elution disk, while gram-positive organisms should be tested with the
0.22 mcg disk.
DIFFUSION TECHNIQUE: For the Kirby-Bauer method of susceptibility testing, a 10
mcg ampicillin diffusion disk should be used. With this procedure, a laboratory
report of "susceptible" indicates that the infecting organism is likely to
respond to PENGLOBE therapy, and a report of "resistant" indicates that the
infecting organism is not likely to respond to therapy. An "intermediate
susceptibility" report suggests that the infecting organism would be susceptible
to PENGLOBE if a high dosage is used or if the infection is confined to
tissues and fluids (e.g., urine) in which high antibiotic levels are attained.
DILUTION TECHNIQUES: Broth or agar dilution methods may be used to determine
the minimal inhibitory concentration (MIC) value for susceptibility of bacterial
isolates to PENGLOBE. Since PENGLOBE per se has no In Vitro activity,
ampicillin powder should be used in a twofold concentration series of the
antibiotic prepared in either broth (in tubes) or agar (in petri plates). Tubes
should be inoculated to contain 104 to 105 organisms/mL or plates "spotted" with
103 to 104 organisms.
INDICATIONS AND USAGE:
PENGLOBE is indicated for the treatment of the following infections when
caused by ampicillin- susceptible organisms:
1. Upper and Lower Respiratory Tract Infections (including acute exacerbations
of chronic bronchitis) due to streptococci (beta-hemolytic streptococci,
Streptococcus Pyogenes), pneumococci (Streptococcus Pneumoniae),
nonpenicillinase-producing staphylococci and H. Influenzae;
2. Urinary Tract Infections due to E. Coli, Proteus Mirabilis, and
Streptococcus Faecalis (enterococci);
3. Skin and Skin Structure Infections due to streptococci and susceptible
staphylococci;
4. Gonorrhea (acute uncomplicated urogenital infections) due to Neisseria
Gonorrhoeae.
Bacteriological studies to determine the causative organisms and their
susceptibility to PENGLOBE (i.e., ampicillin) should be performed. Therapy may
be instituted prior to obtaining results of susceptibility testing. Indicated
surgical procedures should be performed.
CONTRAINDICATIONS:
The use of ampicillin class antibiotics is contraindicated in individuals with a
history of an allergic reaction to any of the penicillin antibiotics and/or
cephalosporins.
WARNINGS:
Serious and occasional fatal hypersensitivity (anaphylactic) reactions have been
reported in patients on penicillin therapy. Although anaphylaxis is more
frequent following parenteral therapy, it has occurred in patients on oral
penicillins. These reactions are more apt to occur in individuals with a history
of penicillin hypersensitivity and/or hypersensitivity to multiple allergens.
There have been reports of individuals with a history of penicillin
hypersensitivity who have experienced severe reactions when treated with
cephalosporins. Before therapy with a penicillin, careful inquiry should be made
concerning previous hypersensitivity reactions to penicillins, cephalosporins,
and other allergens.
IF AN ALLERGIC REACTION OCCURS, THE DRUG SHOULD BE DISCONTINUED AND THE
APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTOID REACTIONS REQUIRE
IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS,
AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS
INDICATED.
PRECAUTIONS:
1. GENERAL: The possibility of superinfections with mycotic or bacterial
pathogens should be kept in mind during therapy. If superinfections occur
(usually involving Aerobacter, Pseudomonas, or Candida), the drug should be
discontinued and appropriate therapy instituted.
As with any potent agent, it is advisable to check periodically for organ system
dysfunction during prolonged therapy. This includes renal, hepatic, and
hematopoietic systems and is particularly important in prematures, neonates, and
patients with liver or renal impairments.
A high percentage of patients with mononucleosis who receive ampicillin develop
a skin rash. Thus, ampicillin class antibiotics should not be administered to
patients with mononucleosis.
2. CLINICALLY SIGNIFICANT DRUG INTERACTIONS: The concurrent administration of
allopurinol and ampicillin increases substantially the incidence of rashes in
patients receiving both drugs as compared to patients receiving ampicillin
alone. It is not known whether this potentiation of ampicillin rashes is due to
allopurinol or the hyperuricemia present in these patients. There are no data
available on the incidence of rash in patients treated concurrently with
PENGLOBE (bacampicillin HCl) and allopurinol. PENGLOBE should not be co-
administered with Antabuse (disulfiram).
3. DRUG AND LABORATORY TEST INTERACTIONS: When testing for the presence of
glucose in urine using Clinitest(TM), Benedict's Solution, or Fehling's
Solution, high urine concentrations of ampicillin may result in false-positive
reactions. Therefore, it is recommended that glucose tests based on enzymatic
glucose oxidase reactions (such as Clinistix(TM) or Testape(TM)) be used.
Following administration of ampicillin to pregnant women a transient decrease in
plasma concentration of total conjugated estriol, estriol-glucuronide,
conjugated estrone and estradiol, has been noted.
4. PREGNANCY CATEGORY B: Reproduction studies have been performed in mice and
rats at PENGLOBE doses of up to 750 mg/kg (more than 25 times the human dose)
and have revealed no evidence of impaired fertility or harm to the fetus due to
PENGLOBE.
There are, however, no adequate and well controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response,
this drug should be used during pregnancy only if clearly needed.
5. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: No carcinogenicity or
mutagenicity studies were conducted. No impairment of fertility and no
significant effect on general reproductive performance was observed in rats
administered oral doses of up to 750 mg/kg of bacampicillin HCl per day prior to
and during mating and gestation. In addition, bacampicillin HCl caused no drug-
related effects on the reproductive organs of rats or dogs receiving daily oral
doses of up to 800 and 650 mg/kg respectively for 6 months.
6. LABOR AND DELIVERY: Oral ampicillin class antibiotics are generally poorly
absorbed during labor. Studies in guinea pigs showed that intravenous
administration of ampicillin decreased the uterine tone, frequency of
contractions, height of contractions, and duration of contractions. However, it
is not known whether use of PENGLOBE in humans during labor or delivery has
immediate or delayed adverse effects on the fetus, prolongs the duration of
labor, or increases the likelihood that forceps delivery or other obstetrical
intervention or resuscitation of the newborn will be necessary.
7. NURSING MOTHERS: Ampicillin class antibiotics are excreted in milk;
therefore, caution should be exercised when ampicillin class antibiotics are
administered to a nursing woman.
8. PEDIATRIC USE: PENGLOBE tablets are indicated for children weighing 25 kg
or more.
DRUG INTERACTIONS:
The concurrent administration of allopurinol and ampicillin increases
substantially the incidence of rashes in patients receiving both drugs as
compared to patients receiving ampicillin alone. It is not known whether this
potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia
present in these patients. There are no data available on the incidence of rash
in patients treated concurrently with PENGLOBE (bacampicillin HCl) and
allopurinol. PENGLOBE should not be co-administered with Antabuse
(disulfiram).
ADVERSE REACTIONS:
As with other penicillins, it may be expected that untoward reactions will be
essentially limited to sensitivity phenomena. They are more likely to occur in
individuals who have previously demonstrated hypersensitivity to penicillins and
in those with a history of allergy, asthma, hay fever, or urticaria.
In well controlled clinical trials conducted in the U.S. the most frequent
adverse reactions to PENGLOBE were epigastric upset (2%) and diarrhea (2%).
Increased dosage may result in an increased incidence of diarrhea. In the same
clinical trials the most frequent adverse effects for amoxicillin were diarrhea
(4%) and nausea (2%).
The following adverse reactions have been reported for ampicillin.
GASTROINTESTINAL: diarrhea, gastritis, stomatitis, nausea, vomiting, glossitis,
black "hairy" tongue, enterocolitis, and pseudomembranous colitis.
HYPERSENSITIVITY REACTIONS: skin rashes, urticaria, erythema multiforme, and an
occasional case of exfoliative dermatitis. These reactions may be controlled
with antihistamines and, if necessary, systemic corticosteroids. Whenever such
reactions occur, the drug should be discontinued, unless the opinion of the
physician dictates otherwise.
Serious and occasional fatal hypersensitivity (anaphylactic) reactions can occur
with oral penicillins. (See WARNINGS.)
LIVER: A moderate rise in serum glutamic oxaloacetic transaminase (SGOT) has
been noted in some ampicillin treated patients, but the significance of this
finding is unknown. In well controlled clinical trials no difference was noted
between ampicillin and PENGLOBE with regard to the incidence of liver function
test abnormalities.
HEMIC AND LYMPHATIC SYSTEMS: Anemia, thrombocytopenia, thrombocytopenic purpura,
eosinophilia, leukopenia, and agranulocytosis have been reported during therapy
with penicillins. These reactions are usually reversible on discontinuation of
therapy and are believed to be hypersensitivity phenomena.
DOSAGE AND ADMINISTRATION:
PENGLOBE tablets may be given without regard to meals.
UPPER RESPIRATORY TRACT INFECTIONS (including otitis media) due to streptococci,
pneumococci, nonpenicillinase-producing staphylococci and H. Influenzae;
URINARY TRACT INFECTIONS due to E. Coli, Proteus Mirabilis, and Streptococcus
Faecalis;
SKIN AND SKIN STRUCTURES INFECTIONS due to streptococci and susceptible
staphylococci:
USUAL DOSAGE
Adults: 1 X 400 mg tablet every 12 hours (for patients weighing 25 kg or more).
Children: (>/= 25kg) 25 mg/kg per day in 2 equally divided doses at 12 hour
intervals.
IN SEVERE INFECTIONS OR THOSE CAUSED BY LESS SUSCEPTIBLE ORGANISMS:
USUAL DOSAGE
Adults: 2 X 400 mg tablets every 12 hours (for patients weighing 25 kg or
more).
Children: (>/= 25 kg) 50 mg/kg per day in 2 equally divided doses at 12 hour
intervals.
LOWER RESPIRATORY TRACT INFECTIONS due to streptococci, pneumococci,
nonpenicillinase- producing staphylococci, and H. Influenzae:
USUAL DOSAGE
Adults: 2 X 400 mg tablets every 12 hours (for patients weighing 25 kg or
more).
Children: (>/= 25 kg) 50 mg/kg per day in 2 equally divided doses at 12 hour
intervals.
GONORRHEA--acute uncomplicated urogenital infections due to N. Gonorrhoeae
(males and females):
1.6 grams (4 X 400 mg tablet plus 1 gram probenecid) as a single oral dose.
No pediatric dosage has been established.
Cases of gonorrhea with a suspected lesion of syphilis should have dark field
examination before receiving PENGLOBE and monthly serological tests for a
minimum of four months. Larger doses may be required for stubborn or severe
infections.
It should be recognized that in the treatment of chronic urinary tract
infections, frequent bacteriological and clinical appraisals are necessary.
Smaller doses than those recommended above should not be used. In stubborn
infections, therapy may be required for several weeks. It may be necessary to
continue clinical and/or bacteriological follow-up for several months after
cessation of therapy. Except for gonorrhea, treatment should be continued for a
minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic
or evidence of bacterial eradication has been obtained.
IT IS RECOMMENDED THAT THERE BE AT LEAST 10 DAYS' TREATMENT FOR ANY INFECTION
CAUSED BY HEMOLYTIC STREPTOCOCCI TO PREVENT THE OCCURRENCE OF ACUTE RHEUMATIC
FEVER OR GLOMERULONEPHRITIS.
************************************************************************